Pharmacokinetics of high‐dose intravenous melatonin in humans

Abstract

This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221,500.0 (185,637.5-326,175.0) pg/mL and 1,251,500.0 (864,375.0-1,770,500.0) pg/mL, respectively; mean (SD) t1/2 was 42.3 (5.6) minutes and 46.2 (6.2) minutes; mean (SD) Vd was 1.6 (0.9) L/kg and 2.0 (0.8) L/kg; mean (SD) CL was 0.0253 (0.0096) L/min · kg and 0.0300 (0.0120) L/min · kg; and median (IQR) AUC0- ∞ , 8,997,633.0 (6,071,696.2-11,602,811.9) pg · min/mL and 54,685,979.4 (36,028,638.6-105,779,612.0) pg · min/mL. High-dose intravenous melatonin did not induce sedation, evaluated as simple reaction times. No adverse effects were reported in the study.

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

“…Indeed, melatonin has a high safety profile, it is usually remarkably well tolerated and, in some studies, it has been administered to patients at very large doses. Escalating doses of melatonin up to 100 mg were devoid of undesirable activity in humans [209,210]. Melatonin (300 mg/day for up to 3 years) decreased oxidative stress in patients with amyotrophic lateral sclerosis [211] with very few undesirable side effects.…”

Melatonin protects the retina from experimental nonexudative age‐related macular degeneration in mice

“…Overall, our results demonstrate that melatonin is capable of significantly preserve visual functions and retinal structure in experimental NE‐AMD. Therefore, despite the well‐known differences between the mouse and human retina, the treatment with melatonin, a very safe compound which lacks proven adverse effects even at high doses in humans, could become a promising therapy to prevent, slow down or even reverse RPE/retinal damages caused by human NE‐AMD.…”

The Effects of Melatonin on Elevated Liver Enzymes during Statin Treatment

“…Andersen et al [68] administered intravenously 10 or 100 mg of melatonin to 12 healthy volunteers, obtaining its maximum serum concentrations of 185,637 and 1,770,500 pg/mL at T1/2, 43.3 and 46.2 minutes, with the absence of any side effects. The same researchers [69] administered orally 10 mg of melatonin to the volunteers and found its maximum serum concentration of 3550 pg/mL at T1/2, 53.7 min.…”